Download NSCLC - Oncimmune

An Improved
C.
1
Chapman ,
A.
TM
EarlyCDT -Lung
2
Murray ,
L.
3
Peek ,
P.
4
Boyle ,
Test Can Be Used To Aid The Detection of Lung
Cancer
J.
2
Allen ,
1Division
C.
2
Parsy-Kowalska ,
P.
5
Maddison ,
2Oncimmune
G.
2
Healey ,
J.
1,2
Robertson
3Oncimmune
of Surgery, University of Nottingham, Nottingham, UK;
Ltd., Nottingham, UK;
LLC, DeSoto, KS, USA;
4IPRI, Lyon, France; 5Department of Neurology, Nottingham NHS Trust, Nottingham UK.
email: [email protected]
PURPOSE
RESULTS
A humoral immune response in the form of autoantibodies to
tumor-associated antigens has been reported in individuals
with evidence of solid tumors.
The addition of MAGE A4 and Hu-D to the EarlyCDT-lung panel
improved the sensitivity of the assay for the detection of lung cancer by
7% with a loss in specificity of only 1%.
These autoantibodies have been shown to be present in the
circulation of individuals with lung cancer, and in some cases
up to 5 years before the cancer presented clinically (1-3).
These antibodies may therefore represent the earliest marker
of carcinogenesis.
The positivity rates for the panel by stage of disease for non-small cell
lung cancer (NSCLC) and for extensive vs limited disease for small cell
lung cancer (SCLC) were similar for all stages.
53
65
(42-85)
66
(43-85)
62
(42-80)
73%
(171)
78%
(138)
59%
(31)
The presence of autoantibodies was evaluated using a semiautomated enzyme-linked immunosorbent assay (ELISA)
method where optical densities (OD) were converted to
calibrated reference units (RU) (1).
Full assay details are described elsewhere (1).
1.5
1.0
53***
(39, 67)
58***
(44, 72)
Matched
Normals
235
% +ve
95% CI
10
(6, 14)
11
(7, 16)
Specificity
235
%
90
89
Positivity defined as the presence of one or more
autoantibodies (panel of 8 Antigens)
(C
3
p5
All Cancer
NSCLC
SCLC
Late Stage
Early Stage
Antigen (Sample Group)
SCLC LD
NSCLC (I)
NSCLC (II)
NSCLC (III)
Frequency of Autoantibodies to Individual TAAs
GROUP
p53
SOX2
CAGE
NY-ESO-1 GBU4-5
Annexin I MAGE A4
Hu-D
All Lung
Cancers
%+ve
(95% CI)
10
(7, 15)
8
(5, 12)
11
(8, 16)
11
(7, 15)
4
(2, 7)
7
(4, 11)
9
(6, 13)
5
(2, 8)
NSCLC
%+ve
(95% CI)
9
(5, 14)
4
(2, 9)
10
(6, 15)
10
(6, 16)
2
(0, 5)
7
(4, 11)
10
(6, 16)
2
(0, 5)
SCLC
%+ve
(95% CI)
15
(7, 28)
21
(11, 34)
17
(8, 30)
13
(5, 25)
9
(3, 21)
8
(2, 18)
6
(1, 16)
15
(7, 28)
Matched
Normals
%+ve
(95% CI)
2
(1, 5)
3
(1, 5)
2
(0, 4)
2
(0, 4)
2
(1, 5)
3
(1, 7)
2
(1, 5)
0
(0, 2)
Specificity
%
98
97
98
98
98
97
98
>99
REFERENCES
For more information: www.oncimmune.com or 888-583.9030
53
% +ve
95% CI
0.5
%+ve with 95% confidence interval (x,y) in each patient group
1. Murray et al Technical Validation of an autoantibody test for lung
cancer. Ann Oncol. 2010;21:1687
2. Boyle et al Clinical Validation of an autoantibody test for lung
cancer. Ann Oncol. 2010 Jul 30 [Epub]
3. Zhong et al Profiling tumor-associated antibodies for early
detection of non-small cell lung cancer. J Thor Oncol 2006;1:51
42***
(34, 49)
% +ve with 95% confidence interval (x,y) in each patient
group. *Denotes p-value relative to normal control results.
Chi-squared analysis *** -p<0.001
0.0
Stages:
NSCLC (n):
Other Normal
Stage I (87), Stage II (54),
Stage III (16), Stage IV (6),
4
266
unknown (15)
72
65
SCLC (n):
(53-81) (38-86)
Limited Disease (26),
50%
70%
Extensive disease (14),
(2)
(185)
unknown (13)
The antigens comprised those in the EarlyCDT-Lung test
(p53, NY-ESO-1, CAGE, GBU4-5, SOX2 and Annexin I) with
the addition of MAGE A4 and Hu-D.
34***
(27, 41)
CLINICAL IMPLICATIONS
The presence of autoantibodies in individuals with lung
cancer may provide an early indication of disease for high-risk
individuals, when the chance of successful treatment would
be greatest.
80
Male %
(n)
178
178
% +ve
95% CI
60
Median
age (range)
235
45***
(39, 52)
40
Group - n
SCLC
38***
(32, 44)
All Lung
Cancers
n
Forest Plot - Sensitivity by Cancer Stage
Patient Details and Clinical Characteristics
NSCLC
235
% +ve
95% CI
Group
SCLC
2.0
Patients with lung cancers (N=235) and age, gender and
smoking matched controls had autoantibodies to eight tumorassociated antigens measured on serum samples taken postdiagnosis but prior to treatment.
ALL Lung
Cancers
PANEL
of 8
20
METHODS
PANEL
of 6
0
The positivity rate for each antigen by histological subtype and
stage of disease are presented.
Panel of 6 - EarlyCDT-Lung Panel
Panel of 8 - EarlyCDT-Lung + MAGE A4 & Hu-D
ELISA Scatter Plots - Examples
p
a
SO 53 )
X2 (N
)
SO (C
a
X
C 2 )
A
G (N
E )
N CA (C
Y- G a
ES E )
N O (N
Y- -1 )
M ES (C
A O a
G -1 )
E
M A (N
A 4 )
G (C
E
A a)
H 4
u - (N
D )
H (C
u- a )
D
(N
)
The addition of two lung cancer associated antigens to this
test was investigated.
Sensitivity for Final Panel Specificity of ~90%
NSCLC
OD @ 650nm
EarlyCDTTM-Lung detects autoantibodies to a panel of six
tumor-associated antigens (TAAs) with a sensitivity of 40%
and a specificity of 90%. EarlyCDT-Lung has been shown to
aid in the detection of both early-stage and late-stage disease
in high-risk individuals.
The positivity rate for individual autoantibody assays ranged in NSCLC
from 2%-10% and in SCLC from 6%-21% with specificity for each
antigen being >96%.
Frequency of Autoantibodies to a Panel of TAAs
Sensitivity at 89% Specificity
Sensitivity at 89% Specificity
CONCLUSIONS
These data confirm that the addition of two new antigens
to the EarlyCDT-Lung panel increased the detection of
all stages of lung cancer giving a sensitivity of at least
45%.
The presence of autoantibodies may provide an early
indication of lung cancer, even in early-stage disease
and may be useful in the management of high-risk
individuals.
Differences in the autoantibody profiles may in the future
be useful in identifying what subtype or stage of lung
cancer a patient is most likely to have.